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Angiotensin II responsiveness after preeclampsia: Translational data from an experimental rat model and early-onset human preeclampsia

van der Graaf, A. M., Toering, T. J., van der Wiel, M. W. K., Frenay, A-R. S., Wallukat, G., Dechend, R., Navis, G., Groen, H., Lely, A. T. & Faas, M. M., Dec-2017, In : Journal of Hypertension. 35, 12, p. 2468-2478 11 p.

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  • Angiotensin II responsiveness after preeclampsia

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DOI

Objective: Formerly preeclamptic women have an increased risk for cardiovascular and renal disease later in life. It is unknown which mechanisms contribute to this increased risk and whether this is induced by preeclampsia or by prepregnancy factors. We hypothesized that the increased risk for cardiovascular disease is partly due to an increased angiotensin II (ang II) responsiveness postpartum and that preeclampsia itself is involved in inducing this increased ang II responsiveness.

Methods: In never-pregnant, formerly healthy pregnant rats and rats with former experimental preeclampsia [experimental preeclampsia model induced by low-dose endotoxin infusion on day 14 of pregnancy; endotoxin-infused pregnant rats (EP-rats)], ang II responsiveness was studied by measuring changes in blood pressure (BP) and proteinuria after chronic ang II infusion with osmotic minipumps (200ng/kg per min). In addition, we measured BP and responses to ang II (0.3, 1.0 and 3.0ng/kg per min) in 18 formerly early-onset preeclamptic, without comorbidities, and 18 formerly healthy pregnant women (controls).

Results: In rats, a significantly higher systolic BP at termination was observed in formerly EP-rats vs. never-pregnant rats after ang II infusion (159.5 29.5 vs. 136.7 16.8; P = 0.049). In response to ang II, there was a significant increase in proteinuria in formerly EP-rats vs. healthy pregnant and never-pregnant rats (P < 0.01 for both). In humans, 1.0 ng/kg per min ang II showed a trend towards an increased mean arterial BP response in formerly preeclamptic women vs. controls (P = 0.057).

Conclusion: Our data show an increased ang II responsiveness following (experimental) preeclampsia and support a role for preeclampsia itself in altered ang II responsiveness postpartum. 

Original languageEnglish
Pages (from-to)2468-2478
Number of pages11
JournalJournal of Hypertension
Volume35
Issue number12
Publication statusPublished - Dec-2017

    Keywords

  • angiotensin II responsiveness, blood pressure, postpartum, preeclampsia, proteinuria, rat model, STAGE RENAL-DISEASE, PREGNANT RATS, AGONISTIC AUTOANTIBODIES, HYPERTENSIVE DISORDERS, ORAL-CONTRACEPTIVES, AT(1) RECEPTOR, AT1 RECEPTOR, ANG-II, WOMEN, RENIN

ID: 46691526